Comparative transcriptome analyses indicate enhanced cellular protection against FMDV in PK15 cells pretreated with IFN-γ

Interferon gamma (IFN-γ) can induce a host antiviral response to foot and mouth disease virus (FMDV) in vivo and in vitro. To elucidate the mechanism of IFN-γ anti FMDV infection in host cells, high-throughput RNA sequencing was analyzed for systemic changes in gene expression profiles in PK15 cells infected by FMDV with or without IFN-γ pretreatment. More than 25 million reads, covering 1.2-1.5 Gb, were analyzed from each experiment panel. FMDV challenge altered the transcription of genes involved in positively and negatively regulating cell death or apoptosis; however, the expected immune suppression response was not obvious. IFN-γ pretreatment combined with FMDV infection normalized the increase in apoptosis. Furthermore, the transcription factors required for IFN-γ functioning, STAT1 and IRF1 were up-regulated by IFN-γ pretreatment and stimulated downstream IFN-stimulated genes (ISGs). These induced ISGs are mainly responsible for antigen processing, antigen presentation or antiviral defense. Interestingly, a synergistic effect on some ISGs, including OAS1, OAS2, MX1, MX2, RIG-I and IFIT1, was observed in the combined treatment compared to the IFN-γ treatment alone. The suggested effects identified by RNA sequencing were consistent with cellular morphology changes and confirmed by related protein markers. This is the first report exploring transcriptome alterations introduced by FMDV infection with or without IFN-γ pretreatment. The identified key host genes that control cell survival in vitro broaden our comprehensive understanding of how IFN-γ inhibits FMDV infection and may shed light on developing improved FMD control approaches.